Jenkins D. and Griffith O. (P.N.A.S. U.S.A., 1986, 83(2), 290-4) have described the antiketogenic and hypoglycaemic properties of aminocarnitine. Other effects are described in Deana R. et al. Biol. Reprod., 1989, 41(5), 949-55, Jensen H et al. Biochim. Biophys. Acta (1990), 1044 (3), 390-3, Nagy I. et al. Pharmacol. Res. (2000), 41(1), 9-17.
Aminocarnitine and its acetyl derivative were described in the U.S. Pat. No. 4,521,432, Takeda Chemical Industries, as a substance capable of inhibiting the degradation of fatty acids, therefore useful as an antidiabetic agent. The substances described in this reference are obtained through the cultivation of strains of Emericella or Aspergillus and the complete synthesis of the aminocarnitine compound as confirmation of the structure of the compound isolated from the strains of micro organisms is also described.
In WO 85/04396, Cornell University, acylated derivatives of aminocarnitine useful in the treatment of diabetes are described, thanks to their activity as inhibitors of carnitine acyltransferase. The acyl derivatives are prepared by starting from aminocarnitine, the preparation of which is provided through the deacetylation of the corresponding acetylaminocarnitine or by starting from 4-bromocrotonate.
U.S. Pat. Nos. 4,767,781 and 4,948,534, related to U.S. Pat. No. 4,521,432, describe further aminocarnitine derivatives, obtainable from the latter.
In the patent application WO 99/59957, ureic-structured derivatives having activities as reversible inhibitors of carnitine palmitoyltransferase are prepared starting from (R)-aminocarnitine.
Numerous processes for the preparation of (R)- and (S)-aminocarnitine are known, which utilize various synthetic methodologies such as the deacylation of the products obtainable through fermentation such as described in U.S. Pat. No. 4,948,534, the use of chiral synthons such as aspartic acid, as described in WO 01/02341, in the name of the applicant, the resolution of a racemic mixture, described in EP 0 402 322. All these processes however have numerous defects such as low productivity, the high costs of some starting material, numerous synthetic steps. An improved process which starts from mesyloxy carnitine methanesulphonate and its transformation into aminocarnitine via the intermediate azidocarnitine has been recently proposed by the applicant, as described in U.S. Pat. No. 5,532,409. In this process, the mesyloxy carnitine methanesulphonate starting material is produced from carnitine in three steps with good yields (approx. 75%), but using a costly reagent such as methanesulphonic anhydride and producing, as a costly refluent, during the course of the synthesis of aminocarnitine, 2-3 moles of aqueous methanesulphonic acid per mole of product. The formation reaction of azidocarnitine is carried out under high dilution and with consequent low productivity; furthermore the solvent used, DMSO, can present problems of partial instability in the alkaline conditions used in the recovery and recycling; the precipitating solvent of the raw azide, ethyl ether, is industrially discouraged, in that it is dangerous. The 10% Pd/C catalyst used in the hydrogenation reaction has a high precious metal content.